The rheumatoid arthritis shared epitope increases cellular susceptibility to oxidative stress by antagonizing an adenosine-mediated anti-oxidative pathway
2007

Rheumatoid Arthritis Shared Epitope and Oxidative Stress

Sample size: 40 publication Evidence: high

Author Information

Author(s): Ling Song, Li Zhanguo, Borschukova Olga, Xiao Liqun, Pumpens Paul, Holoshitz Joseph

Primary Institution: University of Michigan

Hypothesis

Does the rheumatoid arthritis shared epitope increase cellular susceptibility to oxidative stress?

Conclusion

The rheumatoid arthritis shared epitope activates a nitric oxide-mediated pro-oxidative pathway, increasing cellular vulnerability to oxidative damage.

Supporting Evidence

  • Cells with the shared epitope showed increased levels of reactive oxygen species.
  • SE-positive cells had diminished cAMP-dependent signaling.
  • NO production was linked to increased oxidative stress in SE-positive cells.
  • Cells exposed to SE showed higher vulnerability to oxidative DNA damage.

Takeaway

The shared epitope in rheumatoid arthritis makes cells more sensitive to damage from stress, like when they are exposed to harmful substances.

Methodology

The study measured cAMP levels, adenylyl cyclase activity, and protein kinase A activity, and quantified reactive oxygen species and oxidative DNA damage using various assays.

Participant Demographics

The study involved 40 donors, with 32 carrying SE-positive HLA-DRB1 alleles and 8 being SE-negative.

Statistical Information

P-Value

1.4 × 10^-5

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/ar2111

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